Deschanel, with Alyson Hannigan, Jaime King, Minka Kelly, and Katharine McPhee made a video slumber party featured on FunnyorDie.com to promote regular breast cancer screenings for the organization Stand Up 2 Cancer.[8] In recent years, her passion for animal welfare has led her to providing the narration for My Child Is a Monkey and serving as an associate producer on the documentary film How I Became an Elephant.[9] Deschanel ranked number 72 in The 2012 Hot 100 on AfterEllen.[10]

Deschanel is a vegan and a committed supporter of animal rights causes. She can be seen in an Access Hollywood video at the book launch event of Karen Dawn's Thanking the Monkey: Rethinking the Way We Treat Animals, discussing how vegetarian and vegan diets help the environment, and a video on the homepage of the book's website talking about the importance of animal rights.[11] She collaborated with PETA on a video encouraging mothers to raise their children as vegans.[12] In September 2014, she joined the board of directors at Farm Sanctuary.[13][14]

Deschanel was raised Roman Catholic, but is no longer practicing, and has expressed agnostic views, saying "I am more of a spiritual person, if anything, and I am of the belief that we don't know, and I'm not going to pretend that I do."[15]